Neoplastic disease states are widespread and affect a significant portion of the population. These disease states are the subject of intensive research efforts. Unfortunately, despite such efforts and despite some modest successes, the overall control of these disease states has not been satisfactory. Recently a remarkable success was achieved when patients with advanced metastatic cancers were treated with autologous lymphokine-activated killer (LAK) cells and a recombinant-derived lymphokine, interleukin-2. Substantial tumor regression occurred in almost one-half of the patients treated, with complete remission reported in one instance lasting for at least ten months after cessation of therapy. Partial, but less complete, success was achieved in almost all of the other patients treated. Such success is especially significant because the tumors in the treated patients had resisted all previous conventional therapies.
While the success achieved by such therapy is encouraging, the procedure suffers from numerous practical limitations. In particular it is inordinantly expensive, even by the standards of conventional cancer therapy. The expense results primarily from its time consuming nature, requiring weeks of intensive-care and also from the high cost of interleukin-2. In addition, patients undergoing such therapy suffer from numerous, significant, and severe side effects, most notably massive fluid retention, respiratory complications, blood pressure variations and fever.
Applicants have discovered that if an ornithine decarboxylase inhibitor is administered to a patient prior to removal of lymphocytes, during incubation of the lymphocytes with interleukin-2, and also upon administration of the autologous LAK cells and interleukin-2, the therapy is both more effective and requires lesser quantities of the very costly interleukin-2. This improvement results in part from the known ability of an ornithine decarboxylase inhibitor to reduce tumor load, that is to slow down or temporarily arrest tumor growth, but also, from the ability of ornithine decarboxylase inhibitors to enhance interleukin-2 production by helper T cells. The use of applicants' improved therapy is expected to significantly reduce the incidence of untoward side effects and to reduce the cost of this therapy by allowing for the use of lesser amounts of interleukin-2 .